Boveri, Theodor

(b. Bamberg, Germany, 12 October 1862; d. Würzburg, Germany, 15 October 1915)

biology.

The distinguished American cytologist Edmund B. Wilson wrote in a memorial volume to Boveri (1918) that Boveri’s work “enriched biological science with some of the most interesting discoveries and fruitful new conceptions of our time.”¹ When these words appeared in print, Thomas Hunt Morgan’s the ory of the Gene had not yet been published, and evidence for the linear order of genes had not yet been presented. Fifty years later, when the chromosomal basis of heredity had not only been firmly established but had also been successfully elucidated at a molecular level, the fruitfulness of Boveri’s discoveries and conceptions became fully apparent. Many were of primary importance in leading to the concepts of the chromosomal theory of heredity and were brilliant feats of intellectual and experimental analysis.

Boveri was the second of four sons of Theodor Boveri, a physician descended from a family of Frankish origin, and Antonie Elssner Boveri. He attended school in Bamberg from 1868 to 1875, and the Realgymnasium in Nuremberg from 1875 to 1881. In that year he entered the University of Munich, where after a single semester of concentration on historical-philosophical studies, he turned to natural science. His first scientific training was in anatomy; he studied with Carl von Kupffer, whom he also assisted, at the Anatomical Institute in Munich, and he received the doctorate summa cum laude in 1885. His dissertation, on work performed under Kupffer’s guidance, dealt with the structure of nerve fibers.

In 1885 Boveri was awarded a five-year fellowship, the Lamont-Stipendium (later renewed for two years). This enabled him to transfer in 1885 to the Zoological Institute in Munich, the directorship of which had just been assumed by Richard Hertwig. It was Hertwig who drew Boveri’s interest toward research in cell biology, the area in which he was to make his most significant contributions. Boveri began his work with Hertwig in May 1885 and remained at the Zoological Institute until 1893. He was habilitated in zoology and comparative anatomy in 1887; from 1891 to 1893 he was Hertwig’s assistant.

In 1893, at the age of thirty, Boveri became professor of zoology and comparative anatomy, and director of the Zoological-Zootomical Institute, at the University of Würzburg. He remained there essentially for the rest of his life, although, like many of his contemporaries and successors, he made a number of working visits to the Zoological Station at Naples—the first in 1888, the last in 1914. He received invitations to leave Würzburg for other positions; the most noteworthy was the call, in 1912, to become director of the Kaiser Wilhelm Institute for Biology in Berlin-Dahlem, one of the prototypes of modern biological research laboratories. He declined in 1913. In 1897 Boveri had married an American biologist, Marcella O’Grady, who participated in many of his investigations. They had one daughter, Margret, a well-known writer and journalist.

Boveri had a complicated personality. He is said to have had a somewhat turbulent temperament, yet at least in his later years he succeeded in appearing outwardly cool and objectively self-possessed. His satisfaction with his life in Würzburg, and his enjoyment of the very different style of life at Naples, perhaps reflected two conflicting sides of his character. He had a witty sense of humor, but is known to have been a sharp critic. He also was afflicted at times by strong doubts of his own ability, and was as critical of himself as of others.

Like his parents, Boveri had a lively interest in both art and music. He was an exceptionally fine pianist, and music was an integral part of his daily life. His talent in painting was such that when young he had considered becoming a painter; characteristically, however, he eventually became so dubious of his own ability that he showed his paintings only to his closest friends.

Boveri’s uprightness and strength of character, expressed in his daily life and in his high standards of scientific workmanship, profoundly influenced those who worked with him; many of his associates have attested to the fact that he had a particular talent for friendship. Nonetheless, like others with varied talents and demanding standards, Boveri paid a price for his abilities by suffering physical breakdowns. As early as the summer of 1890, troubled by the fact that his father had fallen into debt and that his mother was ill, he himself became ill with what was considered first to be influenza, then neurasthenia. He became so severely depressed that he was unable to work for months. When he recovered, Boveri returned to his laboratory in Munich for the winter semester of 1891. He was frequently ill thereafter, and subject to recurrent depression and to chronic rheumatism. His poor health may have been a primary factor in his decision not to move to the Kaiser Wilhelm Institute; he suffered a serious illness, involving slight paralysis of one side, shortly before giving his final refusal. Deeply troubled by the outbreak of World War I, Boveri suffered a further decline in his already failing health. He was only fifty-three when he died.

Boveri’s mind was clearly analytical, and penetrated to the core of problems that were to become central to twentieth-century biological thought; his work lay at the borderlines of the disciplines that by midcentury would be distinguished as cytology, embryology, and genetics. He once wrote that most of his work was devoted “to the investigation of those processes by which a new individual with particular attributes develops from the reproductive material of its parents.”²

In 1885 Boveri began a brilliant series of studies on the chromosomes. By this time it had been established that the fusion of the nuclei of egg and spermatozoon was an essential feature of fertilization, the fusion nucleus of the fertilized egg giving rise to all the nuclei of the body; hence the nucleus of each body cell contains nuclear substance from both parents. This had led to the conclusion, first expressed clearly in 1884–1885, that the cell nucleus carries the physical basis of heredity. By 1885 it was also known that at nuclear division part of the nuclear substance, the chromatin, forms definite rods, the chromosomes, which are split longitudinally; at cell division, the longitudinal halves of each chromosome had been observed to separate and pass to the two daughter cells. It also had been shown, for some organisms, that the chromosome number is constant for each species; and in 1883–1884 Edouard Van Beneden had made an important discovery in the eggs of Ascaris megalocephala, a roundworm: namely, that the chromosomes of the offspring are derived in equal number from the nuclei of egg and spermatozoon, thus equally from the two parents. The egg of Ascaris is particularly favorable for cytological studies because it has a small number (two or four) of large chromosomes.

Boveri, inspired by the work of Van Beneden, began to carry out his own studies on the eggs of Ascaris in 1885; preliminary reports began to appear in print in 1886 and 1887, and three of his exhaustive cell studies (Zellenstudien), dealing with Ascaris development, appeared in 1887, 1888, and 1890. The first described some aspects of the maturation of the egg and the formation of its polar bodies. The second, on fertilization and cleavage, demonstrated the individuality of the chromosomes, a discovery fundamental to the whole subsequent development of theories concerning the role of the chromosomes in inheritance.

The chromosomes are visible as such in the nuclei only during periods of nuclear division; at other times they are not discernible as separate entities. Inheritance implies continuity; if the chromosomes were to be construed as being involved in heredity, their seeming disappearance during part of the cell cycle presented a great problem. A few investigations by Van Beneden and others, published in the early 1880’s, had suggested that the chromosomes represented continuing elements in the cell, but these were not conclusive. The nuclei of Ascaris show fingershaped lobes at early cleavage stages. By using these lobes as landmarks, Boveri demonstrated the individuality of the chromosomes. His observations were morphological, but his interpretations of them transcended the purely descriptive; he considered the individual chromosomes to be independent entities and emphasized particularly that they were organized structures. Several years later (1904), in a theoretical paper on the nature of the chromatic substance, he compared them to “elementary organisms [that] lead an independent existence within the cell.”³ Wilson wrote in 1918 that Boveri’s theory of chromosome individuality provided the working basis of nearly all cytological interpretations of genetic phenomena; this evaluation still holds.

The third cell study (1890) confirmed and extended the observations previously made by Van Beneden that at fertilization the egg and spermatozoon contribute equivalent sets of chromosomes to the new individual. This study, integrally related to that of chromosome individuality, completed the shift of emphasis from the nucleus as a whole to the chromosomes as the agents of inheritance. Again, in Wilson’s words, it “first pointed the way to a physical explanation of Mendel’s law of heredity and of genetic phenomena generally.”⁴

Among other outstanding discoveries made by Boveri in his early studies on Ascaris was one concerning the role in fertilization of the midpiece of the spermatozoon. In animals, when the nucleus of the fertilized egg divides, a small structure called the centrosome is an integral part of the cytoplasmic apparatus that organizes the separation of the chromosome halves into the two daughter cells. Independently of one another, Boveri and Van Beneden had previously observed the centrosome in cleaving eggs; Boveri, in studies begun on Ascaris in 1887, showed that the centrosome introduced into the egg at fertilization by the midpiece of the spermatozoon provides the division centers for the dividing egg cell and all its progeny.

Boveri was later to consider other aspects of the development of Ascaris, but in the meantime he turned, under the influence of the Hertwigs, to the study of the sea urchin egg. His early investigations on the eggs of Ascaris were largely observational, and it was clear to him that the role of the nucleus as agent of heredity required experimental proof. He could perform experiments on the eggs of the sea urchin that for technical reasons could not be carried out on those of Ascaris. Boveri’s powers of observation as a microscopist were remarkable, and he was also extremely gifted in devising illuminating experiments.

Of his many experiments on sea urchin eggs, several require special mention here. The Hertwigs had shown in 1887 that unfertilized sea urchin eggs could be broken up, by shaking, into fragments that can be fertilized. In 1889 Boveri fertilized nucleated and nonnucleated fragments, and found that both types could develop normally; he found also that occasionally nonfertilized fragments, containing only the egg nucleus, developed normally. This established experimentally the equivalence of the maternal and the paternal nucleus.

In spite of this and other demonstrations of the importance of the nucleus and its chromosomes in development, Boveri remained open-minded as to the possibility that the cytoplasm of the egg might play some role in heredity; accordingly, in 1889 he began experiments that he thought might test this possibility. He attempted to fertilize nonnucleated fragments of one species of sea urchin eggs with spermatozoa of another species. He found that some resultant larvae resembled larvae of the maternal species; others, larvae of the paternal species. Boveri concluded that the former had developed from fertilized nucleated fragments and the latter from fertilized nonnucleated fragments, and interpreted the results as confirming the primary role of the nucleus, as opposed to the cytoplasm, in determining hereditary traits. But there were technical sources of error in the experiments, which Boveri tried vainly to overcome, and it was not until sixty-five years later that the experiments were successfully carried out by Ubisch. The later experiments showed that Boveri’s results were probably correct, at least for the stages at which he terminated the experiments.

Boveri was eventually to demonstrate that the cytoplasm does play an important role in development, if not in inheritance as such, but before proceeding to this demonstration it is appropriate to summarize one further contribution concerning the role of the chromosomes in development and inheritance. This, the proof of the differential value of the chromosomes, was one of Boveri’s most significant contributions. It was not yet known, when Boveri began his work, whether each chromosome contained factors responsible for the totality of development, for all the hereditary qualities of the individual, or whether each chromosome differed from the others in being responsible for only particular hereditary features, the sum of the various hereditary traits being divided among them all. Boveri proved experimentally the validity of the latter alternative.

He had known, as early as 1888, that in Ascaris certain eggs form four rather than two cells at the first cleavage, each cell with a different number of chromosomes. It had been shown that in the sea urchin such eggs could be produced experimentally by double fertilization. When two spermatozoa enter a single egg, the egg may divide into three or four cells at the first cleavage. Boveri ascertained that under such conditions, the chromosomes are almost always divided unequally among the cells. By studying the abnormalities of development of dispermic eggs, and by relating them to abnormal chromosome distribution, he proved in a most ingenious manner that it was “not a specific number, but a specific assortment of chromosomes [that] is responsible for normal development, and this can mean only that the individual chromosomes possess different qualities.”₅ The preliminary report of this investigation was published in 1902, the very year that Walter Sutton called attention to “the probability that the association of paternal and maternal chromosomes in pairs and their subsequent separation during the reduction division… may constitute the physical basis of the Mendelian law of heredity.”⁶ Although Sutton had begun his work independently of Boveri, he stated that he was publishing a description of it in 1902 because of “the appearance of Boveri’s recent remarkable paper on the analysis of the nucleus by means of observations on double-fertilized eggs.”⁷

It was said above that Boveri’s work on fertilization of egg fragments in the sea urchin reflected his interest in a possible role of the cytoplasm in heredity or development. His observations on Ascaris development, begun as early as 1887, later (1904, 1909, 1910) led to an appreciation of the importance of the cytoplasm in nuclear control. The eggs of the roundworm cleave in a unique pattern, and their chromosomes are unusual at early mitoses in that those in the cells at the lower part of the egg, destined to become the germ cells of the larva, exhibit a behavior different from that of those in the remaining cells. In the cells of the germ cell line, the large chromosomes divide typically; when their split halves separate they pass, as they are, to the two daughter cells in several successive mitoses. In the cells at the upper part of the egg, destined to form the body, at the early mitoses each nucleus discards some of the chromatin. This process, called chromatin diminution, was first described in detail for Ascaris; it has subsequently been shown to occur in a very few other animal species.

Boveri found that the number of cells exhibiting chromosome diminution may be altered in dispermic eggs separating into several cells at the first cleavage, and he also found that he could alter it by centrifuging the egg to alter the position of the nuclei in the cytoplasm. He concluded that the cells not undergoing diminution are normally located in a particular zone of cytoplasm, and that the behavior of the chromosomes is determined by the cytoplasm in which the nuclei lie. This was for many years the most cogent demonstration available of the influence of the cytoplasm upon the nucleus. At a time when much emphasis was placed on the overwhelming importance of the nucleus in development, Boveri wrote almost prophetically on the significance of reciprocal interaction between nucleus and cytoplasm.

Chromosome diminution in Ascaris occurs typically only at the upper part of the egg. It is a polar phenomenon. Boveri also wrote a number of pioneering and important papers on the polarity of the developing sea urchin egg. These led to more exhaustive studies by others, beginning in the 1920’s, that demonstrated double gradients in echinoderm embryos. But some of the concepts deriving from Boveri’s own interpretations of polarity, particularly with respect to the lower region of the egg, which he envisioned as a “privileged” region where differentiation begins and whence influence spreads, may have influenced the development of the organizer theory for the amphibian egg.

Boveri made a number of other important contributions; among them was his discovery of the segmental excretory organs in Amphioxus, believed in his day to be an organism close to the type from which vertebrates evolved. More closely related to his chromosomal studies was his development of a theory, published in 1914, that tumor cells may become malignant as a result of abnormal chromosome numbers; he was early to view the tumor problem as a cell problem. He also tried to explain, on the basis of aberrant chromosome distribution, a condition in bees in which male and female characters are mosaically distributed (1915). Significant as these contributions were, Boveri’s primary influence on subsequent biology emanated from his demonstrations of chromosome individuality and his proof of the differential value of the chromosomes, which, again to borrow Wilson’s words, “laid the basis for the cytological explanation of Mendel’s law of heredity.”⁸

NOTES

1. E. B. Wilson, in W. C. Roentgen, ed., Erinnerungen an Theodor Boveri, p. 67.

2. T. Boveri, “Die Potenzen der Ascaris-Blastomeren bei abgeänderter Furchung”. p. 133.

3. T. Boveri, Ergebnisse über die Konstitution der chromatischen Substanz des Zelkerns, p. 90

4. E. B. Wilson, op, cit., p. 71

5. T. Boveri, “Ueber mehrpolige Mitosen als Mittel zur Analyse des Zellkerns,” p. 75

6. W. S. Sutton, “On the Morphology of the Chromosome Group in Brachystola magna,” in Biological Bulletin, 4 (1902), 39.

7.Ibid., p. 24

8. E. B. Wilson., op, cit, p. 76

BIBLIOGRAPHY

I. Original Works. Boveri’s writings include “Ueber die Bedeutung der Richtungskörper,” in Sitzungsberichte der Gesellschaft für Morphologie und Physiologie zu München, 2 (1886), 101–106; “Ueber den Anteil des Spermatozoon an der Teilung des Eies,” ibid., 3 (1887), 151–164; “Ueber die Befruchtung der Eier von Ascaris megalocephala,” ibid., 71–80; “Ueber Differenzierung der Zellkern während der Furchung des Eies von Ascaris megalocephala,” in Anatomischer Anzeiger, 2 (1887), 688–693; “Zellenstudien I. Die Bildung der Richtungskörper bei Ascaris megalocephala und Ascaris lumbricoides,” in Jenaische Zeitschrift für Naturwissenschaft, 21 (1887), 423–515; “Zellenstudien II. Die Befruchtung und Teilung des Eies von Ascaris megalocephala,” ibid., 22 (1888), 685–882; “Ein geschlechtlich erzeugter Organismus ohne mütterliche Eigenschaften,” in Sitzungsberichte der Gesellschaft für Morphologie und Physiologie zu München, 5 (1889), 73–80; “Zellenstudien III. Ueber das Verhalten der chromatischen Kernsubstanz bei der Bildung der Richtungskörper und bei der Befruchtung,” in Jenaische Zeitschrift für Naturwissenschaft, 24 (1890), 314–401; “Die Nierenkanälchen des Amphioxus,” in Zoologische Jahrbücher, 5 (1892), 429–510; “Ueber die Befruchtungs- und Entwicklungsfähigkeit kernloser Seeigeleier und über die Möglichkeit ihrer Bastardierung,” in Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 2 (1895), 394–443; “Ueber das Verhalten der Centrosomen bei der Befruchtung des Seeigeleies nebst allgemeinen Bemerkungen über Centrosomen und Verwandtes,” in Verhandlungen der Physikalischen-medizinischen Gesellschaft zu Würzburg, n.s. 29 (1895), 1–75; “Die Entwicklung von Ascaris megalocephala mit besonderer Rücksicht auf die Kernverhältnisse,” in Festschrift für Carl von Kupffer (Jena, 1899), pp. 383–430; “Die Polarität von Oocyte, Ei und Larve des Strongylocentrotus lividus,” in Zoologische Jahrbücher, Abteilung für Anatomie und Ontogenie der Tiere, 14 (1901), 630–653; “Ueber die Polarität des Seeigeleies,” in Verhandlungen der Physikalischen-medizinischen Gesellschaft zu Würzburg, n.s. 34 (1901), 145–176; “Zellenstudien IV. Ueber die Natur der Centrosomen,” in Jenaische Zeitschrift für Naturwissenschaft, 35 (1901), 1–220; “Ueber mehrpolige Mitosen als Mittel zur Analyse des Zellkerns,” in Verhandlungen der Physikalischen-medizinischen Gesellschaft zu Würzburg, n.s. 35 (1902), 67–90, trans. by Salome Gluecksohn-Waelsch in B. H. Willier and Jane M. Oppenheimer, eds., Foundations of Experimental Embryology (Englewood Cliffs, N. J., 1964), pp. 76–97; “Ueber den Einfluss der Samenzelle auf die Larvencharaktere der Echiniden,” in Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 16 (1903), 340–363, Ergebnisse über die Konstitution der chromatischen Substanz des Zellkerns (Jena, 1904); “Noch ein Wort über Seeigelbastarde,” in Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 17 (1904), 521–525; “Ueber die Entwicklung dispermer Ascariseier,” in Zoologischer Anzeiger, 27 (1904), 406–417, in collaboration with Nettie Maria Stevens; “Zellenstudien V. Ueber die Abhängigkeit der Kerngrösse und Zellenzahl der Seeigellarven von der Chromosomenzahl der Ausgangszellen,” in Jenaische Zeitschrift für Naturwissenschaft, 39 (1905), 445–524; Die Organismen als historische Wesen. Rektoratsrede (Würzburg, 1906); “Zellenstudien VI. Die Entwicklung dispermer Seeigeleier. Ein Beitrag zur Befruchtungslehre und zur Theorie des Kerns,” in Jenaische Zeitschrift für Naturwissenschaft, 43 (1907), 1–292; “Die Blastomerenkerne von Ascaris megalocephala und die Theorie der Chromosomenindividualität,” in Archiv für Zellforschung, 3 , (1909), 181–268; “Ueber die Möglichkeit, Ascaris-Eier zur Teilung in zwei gleichwertige Blastomeren zu veranlassen,” in Sitzungsberichte der Physikalischen-medizinischen Gesellschaft zu Würzburg (1909), 44–48, in collaboration with Mary Jane Houge; “Ueber die Teilung centrifugierter Eier von Ascaris megalocephala,” in Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 30 (1910), 101–125; “Die Potenzen der Ascaris-Blastomeren bei abgeänderter Furchung. Zugleich ein Beitrag zur Frage qualitativ ungleicher Chromosomenteilung,” in Festschrift für Richard Hertwig (Jena, 1910), III, 133–214; “Ueber die Charaktere von Echiniden-Bastardlarven bei verschiedenem Mengenverhältnis mütterlicher und väterlicher Substanzen,” in Verhandlungen der Physikalischen-medizinischen Gesellschaft zu Würzburg, n.s. 43 (1914), 117–135: Zur Frage der Entstehung maligner Tumoren (Jena, 1914), trans. by Marcella Boveri as The Origin of Malignant Tumors (Baltimore, 1929); “Ueber die Entstehung der Eugsterschen Zwitterbienen,” in Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 41 (1915), 264–311; and “Zwei Fehlerquellen bei Merogonieversuchen und die Entwicklungsfähigkeit merogonischer, partiell-merogonischer Seeigelbastarde,” ibid., 44 (1918), 417–471.

II. Secondary Literature. Writings on Boveri are F. Baltzer, Theodor Boveri. Leben und Werk eines grossen Biologen 1862–1915 (Stuttgart, 1962), trans. by Dorothea Rudnick as Theodor Boveri. Life and Work of a Great Biologist 1862–1915 (Berkeley–Los Angeles, 1967); and “Theodor Boveri,” trans. by Curt and Evelyn Stern in Science, 144 (1964), 809–815; W. C. Roentgen, ed., Erinnerungen an Theodor Boveri (Tübingen, 1918); and Leopold von Ubisch, “Theodor Boveri,” in H. Freund and A. Berg, eds., Geschichte der Mikroskopie; Leben und Werk grosser Forscher (Frankfurt am Main, 1963), I, 121–132.

Jane Oppenheimer

Theodor Heinrich Boveri

During his scientific career in Germany in the late 1800s and early 1900s, Theodor Boveri (1862–1915) worked in fields that then had no names. He was a professor of zoology at the universities of Munich and later Würzburg, but in modern terminology he would not be called a zoologist. He was really a cytologist (a scientist who studies cell structure), a geneticist (a scientist who studies heredity), and an embryologist (one who studies organisms at their earliest stages of development).

Boveri made several important discoveries concerning the growth and reproduction of organisms, but the most important one was that chromosomes—threadlike parts of cells that carry what we would now call genetic information during reproduction—were different from one another. In Boveri's words (as quoted on the website of the University of Würzburg's biology department), chromosomes were "independent individuals that retain this independence even in the core of a cell at rest." That insight helped lay the foundation for the entire modern understanding of how traits of an organism are transmitted from parents to offspring.

Boveri grew up in Bamberg, Germany, and except for several sojourns in Naples, Italy, spent his whole life in southern Germany. Despite his Italian last name, his family had lived in Germany's Franconia region for generations. His father Theodor was a doctor who gave up medicine in favor of music and art after his marriage, managing to squander most of a moderate family fortune in the process. Boveri's mother was also artistically inclined, and Boveri himself not only became a skilled pianist and painter but also exhorted his students to take special care with the prose and drawings of their scientific papers. One of his students, quoted in Fritz Baltzer's biography Theodor Boveri: Life and Work of a Great Biologist, recalled that Boveri returned the first draft of one of his papers with the comment "You must now treat it as a work of art."

Boveri attended elementary schools in Bamberg and went on to the Realgymnasium, school in Nürnberg, studying Latin and ancient Greek in addition to science and graduating in 1881. He went on to the University of Munich, living in a sort of glorified dormitory called the Maximilianeum that was reserved for top graduates of southern Germany's secondary schools, served as a pipeline to top academic and governmental jobs, and came with free room and board. This high-powered program allowed Boveri to find his true calling; whereas many European students followed (and still do follow) predetermined courses of study, Boveri started out studying history and philosophy but switched to natural science during his first year.

Won Seven-Year Fellowship

With his family's deteriorating finances in mind, he took anatomy courses and finished a Ph.D. degree in that field in 1885. (In the German educational system, a Gymnasium lies somewhere between high school and college levels in the U.S.) Boveri's doctoral thesis was called Beiträge zur Kenntnis der Nervenfasern (Contributions to the Study of Nerve Fibers). His work was recognized as exceptional by faculty at the university, who nominated him for a scholarship, the Lamont Fellowship, that gave him the opportunity to continue study and research and ended up supporting him financially for a period of seven years. This gave Boveri the chance to change his focus once again to the subject that fascinated him the most deeply, biology. And he did not let his faculty supporters down.

Working in the laboratories of the university's zoology department, Boveri plunged into one of the hottest areas of biological research at the time. As with many other scientists, his greatest discoveries were accomplished while he was still relatively young. The scientific understanding of the reproduction of organisms had taken great strides during the years when Boveri was completing his education. Investigators had established that when fertilization occurred, the nuclei of the male sperm and female egg cells fused to form a new nucleus containing material from both, and that this process was central to heredity. The existence of chromosomes was known as well, but the big picture of exactly what happened when sperm and egg united was murky.

Building on the work of the Belgian biologist Edouard van Beneden, Boveri filled in an important part of the picture. His work was done using the comparatively simple organism of the horse roundworm Ascaris megalocephala, which had only a few chromosome pairs. Chromosomes themselves were visible only during mitosis or cell division, and scientists were unsure of the exact role they played at different stages of the reproduction process. But Boveri noticed that the cells of this roundworm showed certain lobes or bulges as they divided, and he kept track of the details of these lobes as new cells were formed from an original cell. What he found was that the lobes seemed to recur in the same order on the surfaces of the new cells, suggesting not only that the chromosomes were present and active throughout the process, but also that they were individual entities whose sequence was important.

This discovery was entirely consistent with what Boveri's friends and associates knew of his particular character as a scientist. He was an observer who combined a scientist's rigor with an artist's eye. "When I sit down at the microscope, I suspend belief," Boveri said (according to his student Fritz Baltzer), and his scientific breakthroughs were based on careful reasoning, working with data obtained from detailed visual observations made without preconceptions.

Published Chromosome Observations

Boveri's discoveries about roundworm cell development were published in installments between 1885 and 1890; the centerpieces were three Zellenstudien (Cell Studies), of which the second (1888) contained his important chromosome observations. The third study extended the observations Boveri made in the second, confirming van Beneden's guess that egg and sperm contribute equal numbers of chromosomes to the new fused nucleus or zygote. He also clarified the role of a structure, which he termed the centromer or centrosome, that formed a temporary center between the halves of a dividing cell. American cytologist Edmund B. Wilson, a student of Boveri's and one of the great biologists of the 20th century, noted that Boveri's experiments provided a working model for almost all cell-based interpretations of genetic phenomena.

During the winter of 1887 and 1888, Boveri worked at a zoological research station in Naples, Italy, operated by the German scientist Anton Dohrn and pleasantly situated on a beach at the city's edge. For Boveri the trip was the beginning of a lifelong love affair with the ancient and scenic southern Italian city—or love-hate affair, for even then Naples was a chaotic place filled with street people and small-time con artists. Boveri would return to Naples in 1889, 1894, 1896, 1901, 1905, 1910-12, and 1914.

Boveri's name was well known in German scientific circles by this time, and in 1887 he had passed his Habilitationsschrift examinations, a kind of postdoctoral dissertation defense that qualified him to teach in a German university. In 1891, as the expiration of his long scholarship approached, Boveri was offered the post of Assistant in the Zoological Institute of the University of Munich by his longtime advisor, Professor Richard Hertwig. Although the post did not allow him to focus full-time on his own specific research interests, he accepted; his father was suffering from what became a terminal illness, and he faced the need to become financially independent. In the fall of 1892, however, a prized zoology professorship at the University of Würzburg became vacant, and Boveri was named to the post the following March. The only cloud on his horizon was the recurrence of an illness, variously described as influenza or neurasthenia, that had begun to trouble him in 1890.

Married American Professor

At Würzburg, Boveri began to attract top students, some of them German but others visitors from foreign countries. One of his students was an American woman, Marcella O'Grady, who was a professor at Vassar College in Poughkeepsie, New York. Her scientific activities stirred up some controversy in the generally all-male world of the German university community, and Boveri's mother was not pleased by her son's growing friendship with his American colleague. Nevertheless, the pair were married in Boston on October 5, 1897, and the new Mrs. Boveri became an active participant in her husband's scientific endeavors. She became well versed in the development of sea urchin embryos, a subject Boveri had begun to study on the beach in Naples, and in 1903 she published a paper of her own on the subject. The couple had one daughter, Margret.

Other famous foreign biologists who came to study with Boveri included Edmund Wilson and Nettie Stevens, whom Boveri (according to the University of Würzburg biology website) disliked and called a "bloodsucker." His appeal to top-flight graduate students was not hard to explain, for confirmations of his observations regarding chromosome individuality came thick and fast after he had pointed investigators in the right direction (and after the work of the unknown Austrian monk Gregor Mendel was rediscovered in 1900 after having been buried in an obscure publication for 34 years). Some of those confirmations came from Boveri himself; he remained active as a scholar for the rest of his life, even as the crush of teaching and administrative responsibilities at the university grew greater.

In 1902 he published a paper summarizing the results of experiments in which he intentionally double-fertilized sea urchin eggs. Boveri surmised correctly that divisions of the egg cells in this situation would tend to leave the new divided cells with unequal numbers of chromosomes, and he observed that the sea urchin embryos that developed after this double fertilization were abnormal. Thus he had further evidence that specific chromosome sets were necessary for the reproduction of organisms. Boveri also hypothesized that cancers resulted from malfunctions in the genetic material of cells, an important step in identifying the nature of a disease that at the time was not well understood. He published many other papers through the 1900s and the first part of the 1910s dealing with cell structure and differentiation.

Boveri had an energetic, even feverish attitude toward his own research and often demanded the same from his students. It was only illness that finally slowed him down. In 1912 he was considered for the directorship of one of Germany's top scientific institutions, the Kaiser Wilhelm Institute for Biology in Berlin, but turned the position down after flare-ups of his intermittent ailments left him partially paralyzed on his right side. He was also distressed by the outbreak of World War I, during which he supported the German cause but correctly foresaw the war's unfavorable outcome. His health deteriorated further. "My wife has from the beginning maintained that the war has made me ill, and perhaps there is something in it," he wrote in a letter quoted by Baltzer. "So many people are dying unexpectedly these days." Gall bladder surgery failed to improve his condition, which manifested itself in fever and lung inflammation. He died on October 15, 1915, and was eulogized by several of the scientists who would soon build on his discoveries and create new branches of science.

Books

Baltzer, Fritz, Theodor Boveri: Life and Work of a Great Biologist (translated from the German by Dorothea Rudnick), University of California Press, 1967.

Gillispie, Charles Coulston, editor in chief, Dictionary of Scientific Biography, Scribner's, 1970.

World of Anatomy and Physiology, Gale, 2002.

Online

"Theodor Boveri, 1862-1915," DNA from the Beginning, http://www.dnaftb.org/dnaftb/concept–8/con8bio.html (January 15, 2005).

"Theodor Boveri, 1862-1915," University of Würzburg Biozentrum, http://www.biozentrum.uni-wuerzburg.de/about/boveri.html.en (January 15, 2005).